Endocrine Abstracts (2004) 7 P223

11beta-hydroxysteroid dehydrogenase type 1 and the production of cerebrospinal fluid

S Rauz1,2, EA Walker2, JW Tomlinson2, SV Hughes2, PJ Wood3, PM Stewart2 & PI Murray1


1Ophthalmology, Division of Immunity and Infection, University of Birmingham, Birmingham, UK; 2Endocrinology, Division of Medical Sciences, University of Birmingham, Birmingham, UK; 3Regional Endocrine Unit, Southampton General Hospital, Southampton, UK.


The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain, which then drains principally into the dural sinuses. The balance between production and drainage, in part, facilitates a normal intracranial pressure. The secretion of sodium and anions by the CP, creates an osmotic gradient driving the movement of water into the ventricles. This mechanism is analogous to that found in the ocular ciliary epithelium and the production of aqueous humour: a clear fluid vital to the avascular and transparent structures of the eye. In this system, our data has shown that 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), by activating cortisol (F) from cortisone (E), is a novel mediator of ciliary epithelial sodium transport. Additionally F levels exceed those of E in the aqueous humour, indicating a functional 11beta-HSD1.

Cortisol concentrations in the CSF increase with age irrespective of plasma levels, and are linked to specific genotypes of Alzheimers disease. In post-menopausal women, CSF becomes depleted of oestrogens and dominated by cortisol. This study was designed to assess whether corticosteroid mechanisms, similar to those found in the ocular ciliary epithelium, were present in the CP.

Radioimmunoassay of CSF and plasma from three New Zealand White Albino Rabbits revealed F:E ratios of 22.4 and 11.3 respectively, defining a cortisol generating system within the CP. Enzyme assays conducted on isolated CP, confirmed predominant oxo-reductase activity, and immunohistochemistry on 3micrometre thick formalin-fixed paraffin embedded sections established expression of 11beta-HSD1. These data suggest that 11beta-HSD1 may have a role in CSF production, and relative expression of this isozyme may represent an underlying mechanism of neuroendocrine disease.

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